Acetonitrile → 8-Chloro-2-(4-fluorophenyl)imidazo[1,2-A]pyrazine

温度

45 °C

Into a 1-Neck round-bottom flask was added 2-bromo-1-(4-fluorophenyl)ethanone (125 g, 564 mmol) and 3-chloropyrazin-2-amine (128.9 g, 965.2 mmol) followed by ACN (750 mL). The mixture was stirred at reflux for about 24 h. The reaction mixture was cooled to about 45° C. before the solvent was removed in vacuo to yield a brown solid. The brown solid was suspended in water (500 mL) and basified, whilst stirring, with 2.5N NaOH (500 mL). The mixture was then stirred for about 30 min then re-acidified with 5N HCl (300 mL) and extracted with DCM (5×1000 mL). The combined organic layers were filtered from the insoluble material, washed with water (750 mL), followed by washing with 2.5N HCl (4×750 mL), 2.5N NaOH (500 mL) and water (2×500 mL), then dried over MgSO4 and filtered. The filtrate was eluted through a Florisil® pad (3 inch diameter×3 inch depth), washing with repeated amounts of DCM until no product detected by TLC. The organic solvent was removed in vacuo to yield a yellow solid, which was suspended in 2-propanol (500 mL) at about 80° C. for about 15 min and then cooled to about 30° C. The solid was filtered, washing with petroleum ether [bp 30-60° C.] (2×100 mL) and heptane (2×100 mL) to remove impurities, dried in vacuo at 45° C. to yield the title compound (78.2 g, 55.4%): LC/MS (Table 1, Method g) Rt=2.48 min; MS m/z: 248.2 (M+H)+.

1. temperatureat reflux for about 24 h
2. customwas removed in vacuo
3. customto yield a brown solid
4. stirringThe mixture was then stirred for about 30 min
5. extractionre-acidified with 5N HCl (300 mL) and extracted with DCM (5×1000 mL)
6. filtrationThe combined organic layers were filtered from the insoluble material
7. washwashed with water (750 mL)
8. washby washing with 2.5N HCl (4×750 mL), 2.5N NaOH (500 mL) and water (2×500 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. washThe filtrate was eluted through a Florisil® pad (3 inch diameter×3 inch depth)
12. washwashing with repeated amounts of DCM until no product
13. customThe organic solvent was removed in vacuo
14. customto yield a yellow solid, which
15. temperaturecooled to about 30° C
16. filtrationThe solid was filtered
17. washwashing with petroleum ether [bp 30-60° C.] (2×100 mL) and heptane (2×100 mL)
18. customto remove impurities
19. customdried in vacuo at 45° C.

ORDレコード

ord-7fe5884bd10349bd88b196342d7e5b58

出典データセット

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07709468B2